We believe that a major strength of Stanford University in this application is its prior interest in treating chronic viral infections which has led to expertise in areas such as virology, viral immunology and pharmacology as well as extensive clinical trials experience. Therefore, it is expected our group can continue to generate new relevant technology, be involved in ACTG core committees in Primary Infection, Pharmacology, Site and Data Management, Protocol Evaluation, Virology and Immunology and thereby produce innovative Phase I and Phase II efforts with new agents as well as be involved in DNA oriented Phase III trials. The first five years of funding utilized the available infected populations in our area particularly in collaboration with Kaiser Foundation Hospital in San Francisco. Now, we recognize that there is a need to study more indigent patients and a new collaboration with a pre-existing clinical research funding consortium will allow us to develop satellite units at Santa Clara and San Mateo County Hospitals. This will increase minority and female involvement and bring more IV drug users and people of color into our program. The Virology Laboratory research is central and unique in performing both a variety of cultures, viral antigen testing and quantitative PCR for viral RNA and DNA methods useful for measuring virus load in vivo. Drug sensitivity tests are being pursued in our current Viral Lab as well for monitoring combination versus monotherapy studies. In addition to studies with all the dideoxy drugs alone and in combination, our group has worked with several CD4 derivatives and a glycosidase inhibitor. Another special focus is our ability to perform Developmental Immunology lab studies measuring lymphocyte functions as well as a variety of immunophenotyping. HLA restricted and natural killer cytotoxicity has been measured during interleukin-2 and gp160 antigen administration to patients with a wide spectrum of HIV disease. Present goals include relating the impact of these new drugs on HIV immunity to changes in virus load. We intend to continue to bring innovative clinical science to bear on infection, but we also must change our patient focus now to bring in more women and minorities as the epidemic changes its pattern making those groups the major targets of infection. Our pharmacology group plans to bring together quantitative viral load markers with careful quantitative pharmacological measurements so as to more effectively individualize therapy to patients. We will also interact more with Stanford's oncologists who are interested in lymphoma to work with them in applying new less toxic anti-idiotype monoclonal technology to non-Hodgkins lymphoma. We will continue our opportunistic infection focus on toxoplasmosis and add MAI and pneumocystis efforts.